Severe acute respiratory syndrome (SARS), caused by a novel coronavirus SARS-CoV, has been spreading rapidly across the globe. Since the first reported cases in late 2002, more than 8,360 people have been infected worldwide with an overall mortality rate of over 9%. Due to the rapid and ease of transmission of the virus via possibly multiple routes of infection, SARS-CoV is a potential agent of bioterrorism with severe health and socioeconomic consequences. For the prevention of a potentially devastating epidemic in the future, a safe and effective vaccine must be developed against the virus. To rapidly develop a vaccine against SARS-CoV, we propose here to utilize and adapt reagents and vaccine strategies we have been developing against HIV-1 and smallpox. The specific aims of the study are: (1) to generate and characterize properties of recombinant viral vectors expressing the SARS-CoV S glycoprotein, (2) to develop a safe, high-throughput neutralization assay against the virus, (3) to characterize biochemical properties of glycosylation site mutants of the S protein, and (4) to evaluate immunogenicity of the S protein in rodents using a "prime-boost' vaccine strategy. While many aspects of the proposed studies are based on proven concepts, many others are based on novel ideas that need to be developed further. Successful completion of these studies would provide potential vaccine candidates against SARS-CoV, reagents for future structure-function analyses of the S protein, and strategies for improving vaccines against other viruses.